111(P-58) Stereochemistry of α-Pyrone-type Natural Products from a Fungus
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In 2000, an α-pyrone-containing natural product, TT-1, was isolated from the ethyl acetate extract of a fungi imperfecti Trichurus terrophilus culture by Fujimoto and co-workers in our laboratory. TT-1 significantly suppressed proliferation (blastogenesis) of mouse spleen lymphocytes stimulated with mitogens, concanavalin A (Con A) and lypopolysaccharide (LPS), with IC_<50> values of 0.7 and 0.5μg/mL, respectively. TT-1 was optical active and had a molecular formula of C_<25>H_<38>O_6, and its planar structure was elucidated as 1 consisting of two principal carbon-chains with an α-pyrone ring on the basis of the spectral data. Almost at the same time, Hayakawa and co-workers reported isolation of rasfonin, a new apoptosis inducer in ras-dependent cells from the fermented mycelia of Talaromyces sp. 3656-A1. The planar structure of rasfonin was identical with that of TT-1 (1). However, the absolute stereochemistry of five chiral centers of 1 remained undetermined. Here we describe the determination of absolute stereochemistry of five chiral centers of 1 as 5R, 6R, 7S, 9R, and 6'S on the basis of synthesis of partial structural units (fragments A and B) of 1 in optically active forms and comparison of their spectral and optical data with those of natural specimens. We first prepared fragment B with 6'S-configuration as shown in Scheme 1. Comparison of the ^1H NMR chemical shift data of synthetic di-(R)- and di-(S)-MTPA esters (7 and 8) with those of di-(R)- and di-(S)-MTPA esters of natural products (9 and 10) suggested that the absolute configuration of C-6' position of 1 was S. On the basis of the analysis of spectral data, it was proposed that H-5 and H-6 were cis and 1,3-dimethyl system at C-7 and C-9 was syn for the relative stereochemistry of fragment A. Two diastereomers (13 and 14) with 5-membered lactone were prepared in optically active forms, and their spectral and optical data were compared with those of a natural specimen (13) with 5-membered lactone derived from 1 to reveal that the diastereomer 13 was completely identical with natural specimen. Fragment A was therefore shown to have 5R, 6R, 7S, 9R-configurations.
